Scleroderma renal crisis is a serious vascular complication most commonly associated with systemic sclerosis. Its occurrence in mixed connective tissue disease is very rare, with 10 cases reported to date. Scleroderma renal crisis pathogenesis involves endothelial injury, intimal proliferation, and arteriolar constriction leading to malignant hypertension and, in many cases, microangiopathic hemolytic anemia. Management focuses on prompt initiation of angiotensin-converting enzyme inhibitors, particularly captopril, to control blood pressure and prevent irreversible renal injury. Despite advances in therapy, many patients progress to end-stage renal disease, necessitating dialysis or kidney transplantation. Emerging therapies, including endothelin receptor antagonists and complement inhibitors, may offer benefit in refractory cases. Awareness of scleroderma renal crisis in mixed connective tissue disease is crucial for early recognition and timely intervention to improve outcomes.

100 years ago in the U.S., tuberculosis was the most common cause of primary adrenal insufficiency (AI) (Addison's disease). Autoimmune adrenalitis is now responsible for 80-90% of AI in this country and Europe; nevertheless today, in the U.S. and certainly abroad, diverse infections can involve the adrenals in both the immunocompetent and immunocompromised and potentially produce AI. Such infections range widely: bacterial (e.g., Mycobacterium tuberculosis, in particular), fungal (e.g., histoplasmosis), viral and even protozoal (e.g., severe Plasmodium falciparum malaria). Suspecting AI, especially if chronic, is not straightforward, delays in AI diagnosis may reach > 6 months in 50%, and 50-75% of patients initially present in overt adrenal crisis. Diagnosing adrenal involvement by an infection may be drawn out, typically requires careful imaging, a thorough infectious disease evaluation, and may require adrenal biopsy.

Clinical trials are indispensable to evidence-based medicine, yet their results may not translate directly to individual patients. This review provides guidance for clinicians attempting to apply trial results to points of care. Using cardiovascular trials as examples, we examine how study design, eligibility criteria, background therapy, dose, endpoint selection, monitoring intensity, adherence, crossover, analysis strategy, and control-group event rates influence interpretation and transportability. We emphasize careful interpretation of composite and net clinical benefit endpoints and outline limitations of propensity-score methods. Cross-trial comparisons of antiarrhythmic therapies demonstrate how differences in populations, endpoint definitions, time origins, and surveillance can produce divergent absolute event rates despite similar therapies or protocols. Finally, we propose questions for clinicians attempting to apply trial outcomes to their patient care practices integrated with the individual patient's characteristics, competing risks, goals, and preferences.

Energy drinks are stimulant formulations, not sports drinks, yet they are increasingly embedded in adolescent athletics, gaming, and social media. Most contain substantial caffeine plus taurine, guarana, and other bioactive ingredients whose combined effects may differ from caffeine alone. Randomized pediatric trials document acute changes in blood pressure, autonomic regulation, and cardiac rhythm at commercially available doses; systematic reviews, poison-center surveillance, and sudden-cardiac-arrest series identify a consistent cardiovascular signal with rare severe events. A trigger-substrate-context model explains how rapid stimulant exposure may destabilize unrecognized electrical or structural vulnerability during exercise, heat, dehydration, illness, sleep loss, or co-exposure to other stimulants. Clinicians should specifically ask about energy drinks by name, quantify total stimulant exposure, identify red-flag symptoms, and counsel minors and susceptible patients to avoid these products. Schools, athletic organizations, manufacturers, and regulators should end youth-facing promotion, require transparent labeling, improve hydration education, and strengthen adverse-event surveillance.

The US continues to lag in health outcomes and equity. In Part 1 of this review, we identified a persistent "Action Gap" as a failure of physician professionalism as defined in the Physician Charter. Competency-Based Medical Education identifies professionalism as an opportunity to reconnect ethical foundations to medical training. Role models like internist Jean Cowsert, MD (1925-1967) and a 7-member Black "Medical Intelligence Group", illustrate how professionalism can transcend rhetoric and become action. Cowsert helped lead hospital desegregation during the implementation of Medicare following the passage of the Civil Rights Act of 1964. She provided information to federal officials investigating hospital noncompliance with federal desegregation mandates. Days after her identity was compromised, she was shot dead. The circumstances were recently reviewed by the Department of Justice under the Emmett Till Crime Act. Cowsert's story, the work of Mobile civil rights leader John LeFlore and his "Medical Intelligence Group", demonstrate how physicians and healthcare advocates bridged the gap between ethics and action during one of the most turbulent periods in American medical history. Their example is relevant to modern debates regarding professionalism.